title: Carcinogenicity studies on MTBE: critical review and interpretation.
abstract: Chronic inhalation of toxic concentrations of MTBE caused renal tubular cell neoplasms in male Fischer 344 rats and hepatocellular adenomas in female CD-1 mice. In Sprague-Dawley rats the oral administration of MTBE was associated with increased incidences of Leydig cell tumors and of lymphomas and leukemias (combined) in males and females, respectively. Neither lymphomas nor leukemias were individually increased in treated females. leydig cell tumors are common in rats and do not predict human responses to drugs and chemicals. Neither MTBE nor its metabolite, t-butyl alcohol, possess mutagenic potential and a second metabolite, formaldehyde, is mutagenic in vitro but in vivo results are equivocal. MTBE-induced neoplasms are most likely produced through a nongenetic mechanism which requires chronic exposure to toxic doses. Because of the intense odor (and taste) of MTBE, humans will not tolerate either air or water concentrations sufficient to produce the cytotoxic precursors required to promote cellular proliferation.
authors.affiliation: Department of Pharmaceutical Sciences, Campbell University, Buies Creek, North Carolina 27506, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Mennear
mesh_terms: D018248:Adenoma, Liver Cell / Q000139:chemically induced; D000280:Administration, Inhalation; D000284:Administration, Oral; D000393:Air Pollutants / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced; D007684:Kidney Tubules / Q000187:drug effects; D007942:Leukemia, Experimental / Q000139:chemically induced; D007984:Leydig Cell Tumor / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity; D009812:Odorants; D010051:Ovarian Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D013649:Taste; D013736:Testicular Neoplasms / Q000139:chemically induced; D014874:Water Pollutants, Chemical / Q000633:toxicity; D020002:tert-Butyl Alcohol / Q000378:metabolism / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D008738:Methyl Ethers; D009153:Mutagens; D012997:Solvents; D014874:Water Pollutants, Chemical; D005557:Formaldehyde; C043243:methyl tert-butyl ether; D020002:tert-Butyl Alcohol